Sendeng-4 Suppressed Melanoma Growth by Induction of Autophagy and Apoptosis.

Rina Du,Minli Yang,Wanying Song,Rina Wu,Shikui Wu,Pengwei Zhao,Haining Gao,Yaoxing Gao,Ho Lin

doi:10.1155/2021/5519973

Abstract

Sendeng-4 is a traditional Chinese medicine that has been successfully applied to anti-inflammatory diseases in clinical practice. Monomers within Sendeng-4 showed promising antitumor activity against lung cancer, colon cancer, and cutaneous cancer. However, potency of Sendeng-4 in melanoma has not been explored. This study aims to explore the potential application of Sendeng-4 in melanoma treatment. In the present study, we systemically investigate the possibility of Sendeng-4 for treatment of melanoma cancer in vitro by proliferation assay, colony formation, flow cell cytometry, RNA-seq, western blot, and fluorescence-based assay. Our data demonstrated that Sendeng-4 suppresses the proliferation and colony formation capacity of melanoma cells and induces cell cycle block at G2/M phase and eventually cell death. Mechanistically, transcriptome sequencing demonstrates that the PI3K-AKT pathway was significantly inactivated upon Sendeng-4 exposure, which was confirmed by western blot showing decreased phosphorylation of AKT. In addition, decreased BCL-2 expression and increased BAX expression were observed, suggesting programmed cell death via apoptosis. Moreover, LC3-II production as well as autophagosomes formation was observed as demonstrated by western blot and immunofluorescence, indicating elevated autophagy network by Sendeng-4 stimulation. Collectively, we concluded that Sendeng-4 might be used as an anticancer drug for melanoma.

Highlights

Melanoma is one of the most malignant forms of cutaneous cancer, with an increasing incidence since 1970s [1]
BRAF mutations accounts for around 50% of melanomas [6,7,8]. e other risk factors include arsenic, alcohol consumption, and infection. e 5-year survival rates for melanoma patient depends on the stage at which melanoma is diagnosed, for example, the 5-year survival rate for localized melanoma is more than 98%; the rate for metastatic patient is only 22.5%
Our preliminary findings demonstrated that Sendeng-4 suppressed melanoma proliferation in vitro, mainly through induction of cell death by autophagy and apoptosis

Summary

Introduction

Melanoma is one of the most malignant forms of cutaneous cancer, with an increasing incidence since 1970s [1]. Highest risk factors for melanoma include ultraviolet radiation exposure that causes DNA damage and mutations, especially in the lighter skin population and family history of melanoma with genetic instability mutations [3,4,5]. BRAF mutations accounts for around 50% of melanomas [6,7,8]. Combinational strategies including targeted therapy, radiation therapy, and chemotherapy showed promising clinical outcomes, and the improvement of which was further driven by clinical usage of immune checkpoints inhibitors, Evidence-Based Complementary and Alternative Medicine especially in advanced melanoma [10,11,12,13]. Erefore, there is an urgent need to identify new targets and molecular markers associated with melanoma cancer progression Considerable progress has been made in both diagnosis and treatment in melanoma, management of the advanced metastasis melanoma and overcome drug resistance remain a challenge, largely due to lack of understanding of the molecular mechanism for melanoma development. erefore, there is an urgent need to identify new targets and molecular markers associated with melanoma cancer progression

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